Treatment of Acute Promyelocytic Leukemia (APL) by a Combination of All-Trans Retinoic Acid (ATRA) and Chemotherapy

Lee, Je Jung; Byun, Jeong Rae; Kwon, Sang Yong; Park, Moo Rim; Choi, Kyeoung Sang; Lim, Sung Chul; Chung, Ik Joo; Kim, Hyeoung Joon

Abstract

BACKGROUND: All-trans-retinoic acid (ATRA) induces complete remission (CR) in the great majority of patients with PML/RAR -positive acute promyelocytic leukemia (APL). However, it is associated with a rapid rise in leukocytes in one third to half the patients, with potentially fatal "ATRA syndrome". Furthermore, most of the patients relapse with maintenance therapy using ATRA alone or low-dose chemotherapy. In this study, we have analyzed the outcome for APL patients who were treated with ATRA alone or combined with low-dose chemotherapy followed by postremission chemotherapy in Chonnam University Hospital from April 1993 to December 1997.
METHODS
Sixteen patients with newly diagnosed APL were eligible to analysis. Patients received 45mg/m2 ATRA until CR occurred. If initial WBC were above 5,000/microliter, low-dose chemotherapy was concomitantly given, and if during the ATRA therapy WBC were above 5,000/microliter by day 5 or 10,000/microliter by day 10, or 15,000/microliter by day 15, low-dose chemotherapy was added. Four polychemotherapy cycles or allogeneic bone marrow transplantation were given as postremission therapy.
RESULTS
Median age was 34 years (range, 17 to 67). Of 16 APL patients, 15 (93.8%) achieved CR and 1 (6.2%) died of intracerebral hemorrhage. After a median follow-up of 11.5 months (range, 0 to 47), the Kaplan-Meier estimated overall survival (OS) rate was 87.1 +/- 8.6% at 3 year, the event-free survival (EFS) rate was 87.1 +/- 8.6%, 58.0 +/- 24.4% and 29.0 +/- 23.9% at 1 year, 2 year and 3 year, and the disease-free survival (DFS) rate was 92.9 +/- 6.9%, 69.6 +/- 20.7% and 46.4 +/- 23.5% at 1 year, 2 year and 3 year, respectively.
CONCLUSION
The present study suggests that ATRA with or without low-dose chemotherapy followed by postremission chemotherapy is a well-tolerated and effective regimen that is shown to improve the CR rate, reduce a early mortality rate and considerably prolong the overall survival in patients with newly diagnosed APL.